Silymarin, a flavonolignan derived from Silybum marianum, possesses diverse pharmacological activities, including hepatoprotective, antioxidant, anti-inflammatory, anticancer, and cardioprotective. Although clinical trials have shown silymarin is safe at high doses (>1500 mg/day) in humans, the pharmacokinetic studies over the past three decades related to absorption, distribution, metabolism, and excretion of silymarin have revealed poor absorption, rapid metabolism, and ultimately poor oral bioavailability. For optimum silymarin bioavailability, issues of solubility, permeability, metabolism, and excretion must be addressed. An array of methods have been described in recent years that can improve its bioavailability, including complexation with β-cyclodextrins, solid dispersion method, formation of microparticles and nanoparticles, self-microemulsifying drug delivery systems, micelles, liposomes, and phytosomes. This article critically reviews the recent published literature on various techniques for increasing the bioavailability of silymarin.